The State of the Science of Parkinson’s Research

Recently, Todd Sherer, CEO of The Michael J. Fox Foundation (MJFF), Brian Fiske, vice president of research programs at MJFF, and Emily Drabant, 23andMe’s research manager for its Parkinson’s community, sat down and took stock of the recent advances in Parkinson’s research.Their conversation centered around new understandings of the genetics of Parkinson’s disease that could form the building blocks for research over the next decade.Learning more about the role genetics plays in Parkinson’s could provide life changing new treatments for people living with the disease.  Much of the work to this end is currently focused on a particular mutation in the LRRK2 gene. About one in 10,000 people have this particular mutation – G2019S – which is associated with a 50 percent lifetime risk of Parkinson’s compared to about one percent in the general population. While this association is well established, the role the mutation plays in the development of the disease is less clear. Researchers, however, have made some important breakthroughs offering insight into the possible role that LRRK2 plays in developing the disease, as well as how genetics may interact with environmental factors to cause Parkinson’s.LRRK2 and Neuroinflammation Fiske said new data suggests the body’s immune system, particularly the inflammatory response in the brain, may play a key role in the development of Parkinson’s. Inflammation is the body’s response to injury, but the response, particularly an exaggerated immune response, could lead to harmful neuroinflammation. It appears that one component of Parkinson’s is this harmful neuroinflammatory response. Researchers, supported by MJFF, are studying whether the LRRK2 mutation leads to a more exaggerated inflammatory response.  To date, the data are looking very interesting in this direction.

Todd Sherer, PhD

Sherer said that one high level theory is that if this connection is real this could explain why not everyone with the LRRK2 mutation develops Parkinson’s.“To activate the immune system response you need some kind of trigger,” he said. “It may take a trigger to interact with the genetics, but no one has tested for this yet.”LRRK2 And Cellular Pathways Just as in everyday life we accumulate clutter and waste that eventually has to be thrown out, inside our bodies our daily functions produces trash of sorts that has to be cleared out. Our cells actually have a sort of self-cleaning mechanism called “autophagy” that clears out junk protein and other cellular debris.Parkinson’s researchers have found that this process is somehow broken in patients with the LRRK2 mutation. Studies are focused on whether decreased autophagy may make cells in the brain more susceptible to Parkinson’s-related cell death. Researchers want to know if this is a cause for the disease or simply an effect from it, said Fiske.

Brian Fiske, PhD

LRRK2 Clinical Observations Researchers are comparing individuals who have the LRRK2 mutation and Parkinson’s with people who have developed the disease but don’t have the LRRK2 mutation. These patients who have the disease but don’t have the mutation are also known as “idiopathic” Parkinson’s patients. Researchers found that while the disease in these two types patients appears to be very similar, in some cases the LRRK2 patients have somewhat milder symptoms. For instance, the loss of smell is less pronounced in LRRK2 patients.According to Fiske work comparing these patients has also highlighted some other intriguing links that researchers would like to explore.. For example, there is an apparent link between LRRK2 and an increased risk for non-skin cancers. This may have to do with a shared genetic background among people of similar ancestry, for instance, instead of some other causal link, but The Michael J. Fox Foundation’s LRRK2 Cohort Consortium is looking into this connection.Other Genetic Factors for Parkinson’s When exploring the genetics underlying the disease, researchers are still trying to understand why the LRRK2 mutation sometimes doesn’t lead to development of the disease. Scientists also want to know why the age at which a person develops Parkinson’s is so variable, said Sherer. What is clear is that there are other genetic and environmental factors involved.

Emily Drabant, PhD

And while there is a lot of focus on the LRRK2 mutation, other genetic factors are also involved. Last year 23andMe found two new genetic associations with the disease and more recently found a genetic variant, SGK1, that is potentially protective against the disease. Other genetic mutations associated with the disease include one protein primarily found in brain tissue called alpha-synuclein, which is encoded by the SNCA gene. Researchers have found that alpha-synuclein accumulates and clumps together in the brain of Parkinson’s patients. There currently is a clinical trial for a drug that specifically targets these clumps of alpha-synuclein as a way to treat Parkinson’s patients.There are other genetic variants that are also being looked at, and there is a much broader effort to do a sort of “mega” meta-analysis that would develop a master list of common genetic variants associated with the disease. It’s believed that together these genetic variants account for about a quarter of all Parkinson’s cases, but most of those genetic associations have yet to be discovered. 23andMe and MJFF  are part of this large-scale effort. Some of this work may be helped as the cost of exome sequencing and full genome sequencing continues to drop. Most recently an association with a variant in the VPS35 gene was found through exome sequencing. “It’s one of the first PD genes found (through exome sequencing) so it represents a technological turning point away from the classic (genome-wide association study) approaches in the past,” said Fiske. “It seems to play roles in pathways involved in transport of proteins around the cell, but we have little understanding yet of how it might lead to Parkinson’s.”Parkinson’s Indicators Another thrust of the research is into biomarkers that can be used to track the progression of Parkinson’s and may help in early intervention. It could be that looking at alpha-synuclein or another protein called DJ-1 may offer a good way to track the disease. In the case of alpha-synuclein, it might be that detecting clumps of the protein could offer a good measure. There is also the possibility of piggybacking on a technique developed for brain imaging of Alzheimer’s disease. That method, looking at the beta-amyloid protein, could be copied in some way with Parkinson’s patients. Researchers are now able to use a brain scan, called the DATSCAN, to measure dopamine in the brain. But while the scan is good for detecting deficits in people in early stages of the disease, those deficits don’t change significantly after a patient has full-blown Parkinson’s, said Fiske. New imaging technologies could be used not just to diagnose the disease and its progression, but also to test the effectiveness of drug treatment.Finally, while there is a lot of attention focused on treatment, there is also work being done to try to detect Parkinson’s earlier and earlier. Researchers already know that people in Parkinson’s earliest, or “pre-motor” phase, have distinct symptoms, such as loss of smell, sleep problems and constipation. In combination, those symptoms can be a good predictors of Parkinson’s. By identifying those with high risk of developing the disease, it may be easier to target them with new drugs or other therapies to prevent them from ever developing Parkinson’s.Conclusion New understandings of the genetics of PD offers much to be hopeful about. Parkinson’s is an extremely complex disease, but researchers are finding more and more pieces in our effort to complete our understanding of this sometimes puzzling disease. We are lucky to have so many resources to help us do that. This update really only scratches the surface of the work being done to find treatment and a cure for Parkinson’s. We hope to follow up with another update on the promising Parkinson’s research later this year.
  • Karla Taylor

    My dad was an exterminator for 30 years & I am assuming from articles I’ve read that his occupation was a factor in causing this debilitating disease that was diagnosed in his late 60’s. My brother was afflicted with ALS (Lou Gehrig’s Disease) about age 33 after recovering from 2nd & 3rd degree burns a year prior to his ALS diagnosis. I figure he had a higher susceptibility to ALS & his weakened immuned system allowed the ALS to attack his nervous system at such an early age. Do you think he inherited the genetic tendency for this nervous system disorder from our dad?
    Thanks in advance for your response.

    • Hi Karla,

      At this time there is no known link between ALS and PD, but it’s certainly possible there are genetic factors contributing to susceptibility to multiple neurological conditions. There may also be shared environmental factors that influence both diseases. It’s really not well-studied yet!

  • ….in response to this part……”Fiske said new data suggests the body’s immune system, particularly the inflammatory response in the brain, may play a key role in the development of Parkinson’s. Inflammation is the body’s response to injury, but the response, particularly an exaggerated immune response, could lead to harmful neuroinflammation. It appears that one component of Parkinson’s is this harmful neuroinflammatory response.”

    I have to wonder what the role of having Periodontal Disease (gum disease) is as this is known to spike the host response or inflammatory response for the body. You can check the CRP levels in the blood for example and see gum disease increases the CRP levels. As 75-80% of ALL adult patients get periodontal disease at some point in life….(and as we live longer now) I have to wonder what role that gum disease plays for all diseases that are affected by the way the body overreacts to inflammatory response to everyone…but especially in people with these special mutations.

    …Karla Taylor….(do you know if your father had any history of gum disease aka Periodontal disease?)


    What do you think of the STEM CELL work going on to cure this horrible disease?

    I’m pretty sure that Athersys is getting ready to make a huge breakthru anyday. GOOOO Stem cells!

  • sharon lacey

    hello – i was wondering if any research has been done with VITILIGO and if so was there any thing to suggest a link with an auto immune response

  • I have my first appointment with a neurologist at Grady Hospital in Atlanta Ga next week.
    I would love to know your thoughts on working with this doctor to help me assess my health.

    I have “spit” in the cup, and have the LRRK2 marker.

    My main issue is chronic pain. but Parkinson’s is up there.

    Clinical depression treated since age 19

    I am 61 an artist,once earning money, dyslexic, ADHD

    Have some of Parkinson’s wonderful gifts but I am not on meds for it.

    My hope is finding out that some how I can live without pain. And do art because the world is a beautiful place already, but I want to decorate it a bit more.
    I would appreciate any friendly advice on dealing with my first neurology visit.

  • Machelle

    Wow I am finding this really interesting. I found some research several years ago that someone had questioned if Parkinson is some form of auto immune disease in some people. I have the LRRK2 mutation and do have pd. My father also has pd and so did my paternal grandfather. Recently was diagnosed with AIED- auto immune ear disease. ENT and RA said that there is another underlying auto immune disease. Have mega tons of testing and seeing all types of specialists nothing is showing up. I have had huge increases in fatigue and weakness and shakiness since August. I have been asking if any of this can be linked to my PD and have been told no. So I am still on the search.

    I am very glad I participated in 23 and me and am anxious to see where all this research does lead.

  • i have had parkinson’s for10 years.before this i had many bouts of ulcerated colitis , which put me hospital too many times as well a rehab visit. i am wondering if colitis had any thing to do with Parkinson’s ?

    I also was in the 23 and me trial of saliva being released in cup.

    Thank you,

    Dorothy DeSano


  • Doug Manuel

    “There currently is a clinical trial for a drug that specifically targets these clumps of alpha-synuclein as a way to treat Parkinson’s patients.”
    Please send contact information for this trial.
    Thank you.

  • To what degree is delivery holding up the research? The words alpha-synuclein, GDNF, stem cells, genetic analysis, and small molecules to get into the blood brain barrier seem to be key words. Also mitochondria, autoimmunne, inflammation, hormones, and gut sources and pre-pd symptoms are understood.

    I wonder if 23andme could do complete genetic workups on enough pwp to compare; of course you are so generously trying to solve it; but we need our entire genome analyzed. It’s steering your funds to what could only be a wealth of connections and the data would be accurate and wouldn’t rely on a person’s memory. pwp can’t afford it and we have quite a few that have had it as long as Michael. i think it is not unfair to say that 23andme, kinetics, MJFF and Google could afford to provide this testing and that some funding should go to directly studying the inside of pwp bodies before autopsy.

    IT would cost much money, but produce results and be like the pot of gold at the end of the rainbow for pd research; it would debunk myths and false assumptions and lead to so many discoveries.

    Then at the same time, work on delivery systems??
    Trials are not making it and the time and money are wasted. we’re right here….spend it on testing us….it will be well spent on gene discoveries – better than testing a med …it’s safe and could change the world.


  • Ross White

    Interested in mention of vitiligo. I have early onset PD and have recently developed vitiligo, which I understand to be an auto-immune issue as is hyperthyroidism, which I had in my late teens.

  • Anne M

    I am curious as to whether any research has been done to connect Lyme disease as a trigger for Parkinson’s. I was diagnosed with Lyme and Parkinson’s at the same time in 2003 and lab reports showed the Lyme antibodies in both blood and spinal fluid apparently causing inflammation in the brain. I was treated with antibiotics which alleviated many symptoms — fatigue, depression, head aches, migrating pain , and in the early stages improved mobility without any Parkinson’s meds. My neurologist showed me an article linking Lyme with Parkinson’s based on an autopsy of a 63 year old man who had been diagnosed with Parkinson’s but had Lyme throughout his brain.

    Any thoughts or info?


    is there any research on DBS implantation in LRRK2 patients? Would it be any different than for idiopathic type? My PD iis definitely milder than most but I am deveoping a tolerance to the meds and increasing the sinemet has had too many negative side effects that feel worse than the PD itself. Without medication however, I am non ambulatory. I am young onset, in my 40’s and now am in my late 50’s.

    • Hi Brenda,

      Thank you for reading. Unfortunately there isn’t much research on the use of DBS in PD patients carrying the LRRK2 mutation, probably in part because LRRK2 carriers are very rare and DBS is a relatively invasive treatment. 23andMe is definitely interested in exploring the factors influencing different treatments for PD, and we ask our PD participants whether they’ve undergone DBS. Hopefully we’ll learn something!

  • DebiA

    Dear Karla,
    Chock up one more for possible genetic connection between PD and ALS.
    I have early onset PD (onset at 37 ? possibly earlier? I am now 51). My paternal grandfather had ALS for 6 years before dying at xx years.
    My PD came on strong approximately 4 months after the birth of my first child (no obvious inflammation event at that time that I can recall). I did have gestational diabetes during that pregnancy, controlled by diet and exercise, no medication needed; no diabetes after delivery (I have read somewhere that there probably is a link between diabetes and PD.) During all the testing for PD, I was also diagnosed with WPW heart arrhythmia, which was fixed by catheter sonic-ablation surgery (easy fix). I worked for 15 years as a geologist, mostly office work, very little chemical exposure.
    No diabetic problems in Grampa, or the rest of that side of the family, if you are wondering. He did not have any obvious inflammation event prior to onset of ALS as far as I know. He was a farmer in Kansas before the Depression (pre-pesticides?), worked in airplane factories for several years, then was an accountant in Colorado until retirement.

  • Ron J. Campbell

    Do these parkinson’s genetic markers also predict Wolff-Parkinson-White syndrome? It seems to run in my family.

  • rae ann

    My husband was diagnosed with Parkinson’s about 3 years ago. He lost his sense of smell around 10 years ago. We have been married for 55 years(he is 75) He has had restless leg syndrome ever since we got married, but it got worse in his 30’s. He has always had very high cholesterol; once as high as 350. He is Norwegian and Finnish.